Table 1.
Thalidomide in upfront therapy in SMM/indolent MM and symptomatic MM patients candidates for high dose chemotherapy (HDT)
| Trial | Regimen | Thalidomide dose (mg/day) | Duration | Timing | No. of patients | Response (EBMT criteria) | Survival |
|---|---|---|---|---|---|---|---|
| Phase II (Weber et al 2003) | T | 200–600 | Until PD | I/M | 28 | PR 36% | – |
| TD (1) | 100–400 | 3 months | I | 48 | PR + CR 72% | – | |
| Phase II (Rajkumar et al 2003) | T | 200–800 | Until PD | I/M | 29 | PR + MR 66% | – |
| Phase II (Rajkumar et al 2002) | TD (2) | 200–800 | 4 cycles | I | 50 | PR + CR 64% | – |
| Phase II (Wang et al 2005) | TD (1) | 100–300 | 2 cycles | I | 26 | PR + CR 73% | – |
| Phase II (Abdelkefi et al 2005) | TD (1)* | 200 | 3 months | I | 60 | PR + CR 74% | – |
| Phase II (Cavo et al 2005) | TD (2) | 100–200 | 4 months | I | 100 | PR + CR 76% | – |
| Phase III (Rajkumar et al 2006) | TD v D (3) | 200 | 4 cycles | I | 207 | PR + CR 63% v 41% | – |
| Phase II (Wang et al 2005) | VTD (4) | 100–200 | 2 cycles | I | 36 | PR + CR 78% | – |
| Phase II (Zervas et al 2004) | T-VAD doxil (5) | 200 | 4 cycles | I | 39 | PR + CR 74% | 22mos EFS 55% OS 74% |
| Phase II (Schutt et al 2005) | T-VED (6) | 200–400 | Until PD | I/M | 31 | PR + CR 80% | 3y EFS 26% 3y OS 62% |
| Phase II (Hassoun et al 2005) | AD-TD (7) | 100–200 | 2 cycles | I | 45 | PR + CR 84% | - |
| Phase III (Goldschmidt et al 2005) | T with HDT v HDT (8) | 200–400 | Until PD | I/M | 604 | PR + CR 91% v 88% | - |
| Phase III (Hussein et al 2005) | T with HDT (9) | 100–400 | Until PD | I/M | 130 | PR + CR 80% | - |
| Phase III (Barlogie et al 2006) | T with HDT v HDT (10) | 400, 100, 200, 50 | Until PD | I/T/C/M | 668 | CR 62% v 43% | 5y EFS % 56 v 44; similar OS |
| Phase II (Alexanian et al 2002) | TD (1) | 100–300 | Until PD | C | 21 | Further response 57% | Median remission 22 months |
| Phase II (Sahebi et al 2006) | T | 50–400 | Until PD | M | 29 | PR + CR 68% | 2y PFS 49% 2y OS 83% |
| Phase II (Brinker et al 2006) | T | 200 | Until PD | M | 20 | – | Median OS 65 months |
| Phase II (Feyler et al 2005) | T | 50, 100,200,250,300 | Until PD | M | 100 | – | Median PFS |
| 35 months | |||||||
| Phase III (Attal et al 2005) | TP v P v No maintenance | – | Until PD | M | 593 | – | PFS % 56 v 37 v 34 similar OS |
Abbreviations: T, Thalidomide; D, Dexamethasone; P, pamidronate; PD, progressive disease; I, induction; T, transplant; C, consolidation; M, manteinance; EBMT, European Group for Blood and Marrow Transplantation; MR, minimal response; PR, partial response; CR, complete response; EFS, event free survival; PFS, progression free survival; OS, overall survival; TD(1), 20mg/m2 d 1–4, 9–12 and 17–20; TD (1)*, D 20mg/m2 d 1–4, 9–12 and 17–20(odd cycles) d 1–4 (even cycles); TD(2), D 40 mg d 1–4, 9–12 and 17–20 (odd cycles) d 1–4 (even cycles); TD (3), D 40 mg d 1–4, 9–12 and 17–20; VTD(4), D 20 mg/m2 days 1–4, 9–12, and 17–20, v 1.3 mg/m2 (15 patients), 1.5 mg/m2 (11), and ≥1.6 mg/m2 (10); T-VAD doxil (5), Vincristine 2 mg i.v. day 1, Liposomal doxorubicin 40 mg/m2 i.v. day 1, D 40 mg days 1–4; T-VED (6), Vincristine 1.5 mg i.v. day 1, Epirubicin 30 mg/m2 i.v. days 1–2, D 20 mg/m2 days 1–5; AD-TD (7), Doxorubicin 9 mg/m2 i.v. d 1–4, D 40 mg d 1–4, 9–12 and 17–20; after 3 AD cycles, T 100–200 mg d 1–28, D40 mg d 1–4, 9–12 and 17–20, (8) HOVON -50/GMMG-HD3. (9) SWOG 0204. (10) Total Therapy 2.